He was previously the military commander of the Pathet Lao rebellion. On its takeover of the Laotian government in 1975 he became minister of defense, commander of the army, and a deputy prime minister. On the creation of a presidential republic in 1991 he became prime minister, succeeding party leader Kaysone Phomvihane, who became president. General Khamtai Siphandon became party leader on Kaysone's death, and later succeeded Nouhak Phoumsavanh as president.
The republic’s first constitution was endorsed in August 1991 and Gen KhamtaySiphandon, former vice premier and defence minister, became the new premier.
KhamtaySiphandon was unanimously re-elected as party chairman by the PPPL at its sixth congress in March 1996.
The 99-member National Assembly, elected in December 1997 and dominated by the PPPL, elected the outgoing prime minister and party chairman, KhamtaySiphandon, to succeed the 84-year-old Nouhak Phoumsavan as president.